A Study of Pembrolizumab in Patients With Neuroendocrine Tumors

NCT02939651 | Completed Phase 2 Results DMC

• 1 other identifier: GI-087
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to test if pembrolizumab is safe and effective for treating patients with metastatic high-grade neuroendocrine tumors who have failed platinum based chemotherapy.The study drug, pembrolizumab has been FDA approved for treating a type of skin cancer called melanoma and for metastatic non-small cell lung cancer. However, it is not approved for treatment of metastatic high-grade neuroendocrine tumors.

Conditions

Neuroendocrine Tumors

Keywords

Metastatic; High grade

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  To estimate objective response rate (ORR), using RECIST 1.1, in previously treated metastatic High Grade Neuroendocrine Tumors (HGNET) patients treated with pembrolizumab monotherapy. The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria will be used for objective tumor response assessment: Complete Response (CR):Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

  Upto 3 years

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Upto 3 years

• Overall Survival

  Upto 3 years

• Frequency With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  Upto 3 years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Monotherapy with PD-1 antibody pembrolizumab

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab given intravenously at a fixed dose of 200mg every 3 weeks

Also known as: Keytruda, MK-3475

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic, high grade NET (Ki67 \>20%), excluding any high grade NETs of large or small cell type of lung/thymus origin and merkel cell carcinoma
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 12.0
• Has received prior therapy with at least 1 platinum-containing regimen
• Age \> 18 years.
• ECOG performance status 0 or 1
• Patients must have normal organ and marrow function
• Female participants of childbearing potential must have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication). They should also be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

You may not qualify if:

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Prior anti-cancer therapy with a monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events (improved to grade 1 or less) due to mAbs administered more than 4 weeks earlier.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (12 weeks for measurable sites of CNS disease) prior to study Day 1 or not recovered from adverse events (improved to grade 1 or less) due to a previously administered agent. Note: Subjects with neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Known additional malignancy that is progressing or requires active treatment except superficial malignancies of the skin and in situ cervical cancer
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active non-infectious pneumonitis.
• Active infection requiring systemic therapy at enrollment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has received a live virus vaccine within 30 days of planned start of trial treatment.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening period through 120 days after the last dose of trial treatment
• Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
• Known history of human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, United States

Location

Related Publications (1)

• Vijayvergia N, Dasari A, Deng M, Litwin S, Al-Toubah T, Alpaugh RK, Dotan E, Hall MJ, Ross NM, Runyen MM, Denlinger CS, Halperin DM, Cohen SJ, Engstrom PF, Strosberg JR. Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. Br J Cancer. 2020 Apr;122(9):1309-1314. doi: 10.1038/s41416-020-0775-0. Epub 2020 Mar 10.

  PMID: 32152503 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Pembrolizumab can be safely administered to patients with G3NENs but has limited activity as a single agent. Further research to identify active combination therapies should be considered.

Results Point of Contact

• Title: Namrata Vijayvergia
• Organization: Fox Chase Cancer Center

Namrata.Vijayvergia@fccc.edu

+1 215-214-4283

Study Officials

• Namrata Vijayvergia, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2016
• First Posted: October 20, 2016
• Study Start: October 26, 2016
• Primary Completion: February 1, 2018
• Study Completion: March 1, 2020
• Last Updated: March 9, 2021
• Results First Posted: March 9, 2021

Record last verified: 2021-02

Locations

US (2)